Using the isolated and perfused liver of rats, we investigated the effect of starvation on hepatic glucose output and hepatic insulin extraction. The rats were starved for 72 h. The intestines of fed and starved rats were isolated and perfused, and portal venous effluent (PVE) was collected. The liver of fed and starved rats was perfused with synthetic medium or PVE containing 100 mg/dl glucose and 100 µU/ml insulin. Fractional uptake of insulin and reduction in glucose output by the perfused liver were almost the same in all groups. These results suggest that the removal and action of insulin in the liver were not altered by short-term starvation in rats